Open AccessTwist1 accelerates tumour vasculogenic mimicry by inhibiting Claudin15 expression in triple‐negative breast cancer
Author(s) -
Zhang Danfang,
Sun Baocun,
Zhao Xiulan,
Sun Huizhi,
An Jindan,
Lin Xian,
Zhu Dongwang,
Zhao Xueming,
Wang Xudong,
Liu Fang,
Zhang Yanhui,
Liu Jiameng,
Gu Qiang,
Dong Xueyi,
Qiu Zhiqiang,
Liu Zhiyong,
Qi Hong,
Che Na,
Li Jing,
Cheng Runfen,
Zheng Xu
Publication year - 2020
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.15167
Subject(s) - vasculogenic mimicry , triple negative breast cancer , cancer research , biology , motility , twist transcription factor , breast carcinoma , breast cancer , cancer , epithelial–mesenchymal transition , metastasis , microbiology and biotechnology , genetics
The up‐regulation of EMT regulator Twist1 has been implicated in vasculogenic mimicry (VM) formation in human triple‐negative breast cancer (TNBC). Twist1 targets the Claudin15 promoter in hepatocellular carcinoma cells. Claudin family members are related with TNBC. However, the relationship between Claudin15 and VM formation is not clear. In this study, we first found that Claudin15 expression was frequently down‐regulated in human TNBC, and Claudin15 down‐regulation was significantly associated with VM and Twist1 nuclear expression. Claudin15 down‐regulation correlated with shorter survival compared with high levels. Claudin15 silence significantly enhanced cell motility, invasiveness and VM formation in the non‐TNBC MCF‐7 cells. Conversely, an up‐regulation of Claudin15 remarkably reduced TNBC MDA‐MB‐231 cell migration, invasion and VM formation. We also showed that down‐regulation of Claudin15 was Twist1‐dependent, and Twist1 repressed Claudin15 promoter activity. Furthermore, GeneChip analyses of mammary glands of Claudin15‐deficient mice indicated that Claudin18 and Jun might be downstream factors of Twist1‐Claudin15. Our results suggest that Twist1 induced VM through Claudin15 suppression in TNBC, and Twist1 inhibition of Claudin15 might involve Claudin18 and Jun expression.